Improved prostate delineation in prostate HDR brachytherapy with TRUS‐CT deformable registration technology: A pilot study with MRI validation

Abstract Accurate prostate delineation is essential to ensure proper target coverage and normal‐tissue sparing in prostate HDR brachytherapy. We have developed a prostate HDR brachytherapy technology that integrates intraoperative TRUS‐based prostate contour into HDR treatment planning through TRUS‐CT deformable registration (TCDR) to improve prostate contour accuracy. In a perspective study of 16 patients, we investigated the clinical feasibility as well as the performance of this TCDR‐based HDR approach. We compared the performance of the TCDR‐based approach with the conventional CT‐based HDR in terms of prostate contour accuracy using MRI as the gold standard. For all patients, the average Dice prostate volume overlap was 91.1 ± 2.3% between the TCDR‐based and the MRI‐defined prostate volumes. In a subset of eight patients, inter and intro‐observer reliability study was conducted among three experienced physicians (two radiation oncologists and one radiologist) for the TCDR‐based HDR approach. Overall, a 10 to 40% improvement in prostate volume accuracy can be achieved with the TCDR‐based approach as compared with the conventional CT‐based prostate volumes. The TCDR‐based prostate volumes match closely to the MRI‐defined prostate volumes for all 3 observers (mean volume difference: 0.5 ± 7.2%, 1.8 ± 7.2%, and 3.5 ± 5.1%); while CT‐based contours overestimated prostate volumes by 10.9 ± 28.7%, 13.7 ± 20.1%, and 44.7 ± 32.1%. This study has shown that the TCDR‐based HDR brachytherapy is clinically feasible and can significantly improve prostate contour accuracy over the conventional CT‐based prostate contour. We also demonstrated the reliability of the TCDR‐based prostate delineation. This TCDR‐based HDR approach has the potential to enable accurate dose planning and delivery, and potentially enhance prostate HDR treatment outcome.


| INTRODUCTION
High-dose-rate (HDR) brachytherapy has been established as an effective treatment for localized prostate cancer over the past two decades. 1,2 Modern HDR prostate brachytherapy, utilizing the most advanced imaging and computer technology, is able to provide high levels of local and biochemical control for intermediate-to high-risk prostate cancers. [3][4][5] There is a consensus today that transrectal ultrasound (TRUS) guided CT-based HDR brachytherapy is most common approach for prostate HDR brachytherapy. [6][7][8][9][10] However, one of the main challenges of CT-based HDR brachytherapy is to accurately contour the prostate in CT images due to the poor soft-tissue contrast. 11,12 We have recently developed an approach to improve the accuracy of the prostate delineation utilizing intraoperative TRUS-based prostate contour and TRUS-CT deformable registration (TCDR). 13,14 Studies have shown that CT-based prostate contours often overestimate the prostate volumes by over 30%, due to the following issues: tendency to include portions of neurovascular bundles; poor definition of the interface between the posterior prostate edge and the anterior rectal wall; and difficulties distinguishing the lower limit of the prostate apical region because of its close proximity to the pelvic floor muscles and the poor contrast between these two soft tissues. 15 To overcome the inaccuracy of CT-based prostate contour, we propose to incorporate TRUS-based prostate contour, which has been shown to provide accurate prostate volumes. [16][17][18][19] Since HDR catheter insertions are guided by intraoperative TRUS, 3D TRUS images of the prostate can be acquired in the OR, which can be easily integrated into the prostate HDR workflow. Since CT has the advantage of accurate dose calculation and HDR catheter recognition, the TRUS-based prostate contour is transformed onto the CT images using TRUS-CT image registration for dose calculation in the treatment planning. Combining the strength of the CT and TRUS, the TCDR-based HDR approach could represent a substantial improvement in terms of tumor targeting and normal-tissue sparing in prostate HDR brachytherapy.
In this report, we will describe the workflow of the TCDR-based HDR prostate brachytherapy.

2.B | Patient Imaging -MRI, TRUS and CT scans
All patients enrolled received MRI, TRUS, and CT scans of the prostate. All patients had diagnostic MR scans prior to the HDR procedures. In this study, we used prostate contours from the MR images as the gold standard to evaluate the TCDR-based prostate delineation. As compared with CT images, MRI has high soft tissue contrast and clear prostate boundaries. 20 The 3D intraoperative TRUS scan of the prostate was obtained right after the catheter insertions in the operating room and the TRUS images were used for the prostate contour. The CT scan followed the conventional CT simulation protocol for HDR treatment planning. The specific parameters of the MRI, TRUS, and CT scans are described below.

2.B.1 | MRI scan
All patients were scanned in feet-down supine position with a body coil using a 1.5T Philips MRI with a voxel size of 1.00 9 1.00 9 2.00 mm 3 . All prostates were manually segmented from the T2-weighted MR images by an experienced radiation oncologist. To evaluate the performance of the TCDR-defined prostate contour technology, we compared the TCDR-based prostate contours with MRI-defined prostate contours.

2.B.2 | TRUS scan
The patient is scanned in the lithotomy position and a series of parallel axial (transverse) scans are captured from the apex to the base with a 2 mm step size to cover the entire prostate gland plus 5 to 10 mm anterior and posterior margins. For a typical prostate, 30 to 40 TRUS images would cover 60 to 80 mm in the longitudinal direction. In this study, all patients were scanned in the lithotomy position using a HI VISION Avius ultrasound machine (Hitachi Medical Group, Japan) and a 7.5 MHz prostate bi-plane probe (UST-672-5/7.5). The transrectal ultrasound probe was held with a mechanical SurePoint stepper (Bard Medical, Inc., Covington, GA, USA) to allow for a manual stepwise movement along the longitudinal axis. The TRUS voxel size was 0.12 9 0.12 9 1.00 mm 3 for seven patients and 0.12 9 0.12 9 2.00 mm 3 for the remaining nine patients. A radiation oncologist subsequently contours the prostate volumes using these 3D TRUS prostate images. In general, it takes 5 to 10 minutes to contour a prostate volume. Although this may be time consuming, physician's manual contour of the prostate are still the standard practice in the clinic.  using HDR catheters as landmarks, and the TRUS-based prostate volume is integrated into the 3D CT images for HDR treatment planning. In this patient group, 12-16 catheters (mean AE STD:

2.B.3 | CT scan
15.1 AE 1.7) were implanted. After TRUS-CT image registration, the planning system generates a treatment plan, indicating desired locations for treatment catheters, relative treatment times for the dwell positions, and the resulting dose distribution. Before treatment delivery, the catheter positions are checked again to make sure no catheter movements during CT simulation and treatment planning period.
Once satisfactory catheter placement has been confirmed, an iridium-192 source is used to deliver the HDR treatment. Stockholm, Swedish). Observer 1 is the treating radiation oncologist with 15-year experience. Observer 2 is a radiation oncologist with 20-year experience. Observer 3 is a radiologist with 20-year experience. To evaluate inter-observer reliability of the prostate contours, three observers performed CT-based prostate contours as well as the TRUS-based prostate contours which were used to generated TCDRbased prostate contours. Each observer was blinded to other observers' contours. The variations of the CT-based and TCDR-based prostate volumes were calculated for the assessment of inter-observer reliability. To evaluate intra-observer reliability of the prostate contours, observer 1 performed CT-based and the TRUS-based prostate contours twice. The time between the first and second contours was over 3 months, which was long enough to reduce recall bias. Again, the variations of the CT-based and TCDR-based prostate volumes were calculated for the assessment of intra-observer reliability.   technology, the segmented the prostate volume difference between the TCDR-based prostate volumes and the MR-defined prostate volumes were 1.8 AE 7.2% and 2.2 AE 6.3% [ Fig. 5(b2)]. There are no significant prostate volume differences between the two measurements by the same physician (P-value = 0.45). The mean TCDRbased prostate volume of the observer 1 is shown in Fig. 5(b3).

| DISCUSSIONS
We developed a TCDR-based HDR technology, which could significantly improve the accuracy of prostate delineation in prostate HDR brachytherapy. This TCDR-based approach requires the acquisition of 3D intraoperative TRUS prostate images after the HDR catheter insertion which takes 1-3 minutes and can be easily integrated into the conventional HDR workflow. These TRUS images provide more accurate prostate contour than the CT images. This TCDR-based TRUS-CT deformable registration is shown in Fig. 6. Visually, the close match between the gold markers and the HDR catheters in the TRUS and CT demonstrated the accuracy of this TCDR-based method. Note that the 10% difference in Dice coefficient means that the mean surface distance between the MRI-defined and TCDRbased prostate volume is around 0.5-1.0 mm for a typical prostate with 30-60 CC volume. The max surface distance between the MRIdefined and TCDR-based prostate volume is less than 2.0 mm for all patients. We anticipate that a margin of equal or larger than 2 mm would take care of this discrepancy.
The difficulties in defining the prostate contour using CT images are well-known. 15 Many CT prostate segmentation technologies have been investigated in recent years, such as the models-based, [23][24][25] classification-based 26-28 and registration-based 29,30 methods. Most of these segmentation approaches are based on the appearance and texture of the prostate gland on CT images. However, in HDR brachytherapy the frequently used metal or plastic catheters introduce considerable artifacts to the CT images. These artifacts often smear the appearance and texture of the CT prostate images; therefore, these previous methods may not work well for the prostate HDR application. The prostate volume comparisons between the CT-based and MRI-based prostate contours of our study are in agreement with previous studies. In our study, the mean volume ratio between CT-based prostate volumes and the MR-defined F I G . 5. Inter-and intra-observer reliability comparison of the prostate contours. (a1) The inter-observer CT-based prostate volume differences in three observers as compared with the gold standard MRI prostate contour; (a2) the TCDR-based prostate volume difference; and (a3) the mean TCDR-based prostate volume of 3 observers. (b1) The intra-observer CT-based prostate volume; (b2) the intra-observer TCDR-based prostate volume difference; and (b3) the mean intra-observer TCDR-based prostate volume difference.
prostate volumes ranged from 1.11 to 1.45, which is consistent with the results of 1.10 to 1.32 in the previous studies. [15][16][17]31 Many studies have shown that accurate prostate volumes can be obtained with both MRI and ultrasound. 15,19,[32][33][34]